Safety profile of hydroxychloroquine used off-label for the treatment of patients with COVID-19: A descriptive study based on EudraVigilance data

Abstract

At the beginning of the COVID-19 pandemic, worldwide attempts were made to identify potential drugs effective against the COVID-19. Hydroxychloroquine was among the first receiving attention. However, following its use in therapy, it has been shown that hydroxychloroquine was not only ineffective but probably, due to its known side effects, even responsible of increased mortality of patients. The objective of this study was to review the safety profile of hydroxychloroquine used off-label for the treatment of COVID-19. We analyze the reports of suspected adverse drug reactions (ADRs) collected in EudraVigilance, the European database of ADR reports. We collected 2266 reports for 2019 and 6525 for 2020. The most reported ADRs during 2020 were those relating to cardiac, hepatic, renal toxicity such as QT prolongation with 400 cases in 2020 (of which, 345 cases-9.97%-with COVID-19 as a therapeutic indication) versus 1 case only in 2019 (0.01%), long QT syndrome: 38 cases in 2020 (36 as COVID-19 treatment) versus 0 in 2019, hepatitis: 13 cases in 2019 (0.11%) and 132 in 2020, and 32 cases (24, 0.69%) of acute kidney injury in 2020 and only 3 cases in 2019. Moreover, some important vision-related ADRs also increased significantly during 2020, such as retinal toxicity with 92 cases in 2020 versus 7 in 2019. Even though with its intrinsic limitations, our results may be added to the most recent scientific evidence to confirm the unfavorable risk profile of hydroxychloroquine in its off-label use in the treatment of COVID-19 disease.

Keywords: COVID-19; benefit-risk balance; hydroxychloroquine; off-label; safety.

FIGURE 1

Monthly distribution of hydroxychloroquine ADR reports in 2019 and 2020